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Area of Science:

  • Synthetic biology and xenobiology.
  • Genetic code engineering and artificial microbes.

Background:

  • Biology increasingly relies on chemical synthesis, particularly DNA synthesis for synthetic biology (SB).
  • Xenobiology (XB) expands SB by incorporating non-natural building blocks into living cells.
  • Genetic code engineering allows redesigning genes and proteins with non-canonical nucleic acids (XNAs) and amino acids (ncAAs).

Purpose of the Study:

  • To provide a history and evolution of the genetic code within xenobiology.
  • To discuss current efforts and challenges in genetic code engineering, including ncAAs and amino acid reductions.
  • To present a roadmap for directed evolution of artificial microbes using rare sense codons for novel building blocks.

Main Methods:

  • Reviewing the history and evolution of the genetic code in xenobiology.
  • Discussing advancements in genetic code engineering for non-canonical amino acid incorporation and reduction of standard amino acids.
  • Proposing a roadmap for directed evolution of artificial microbes with genetic firewalls.

Main Results:

  • Xenobiology enables the development of novel therapeutic proteins, biocatalysts, and biosafety strategies.
  • Genetic code engineering with ncAAs offers new possibilities for protein and genome redesign.
  • Artificial microbes with 'genetic firewalls' can be evolved to study code evolution and horizontal gene transfer.

Conclusions:

  • Xenobiology and genetic code engineering are powerful tools for creating novel biological solutions.
  • Engineering the genetic code with non-natural building blocks opens new avenues in biotechnology and synthetic chemistry.
  • Directed evolution of artificial microbes is key to understanding fundamental biological processes and developing advanced biotechnologies.